Each year, there are 50,000 new U.S. cases of coccidioidomycosis (Valley Fever). The majority of these illnesses occur as a result of endemic exposure in Arizona and California to residents, tourists, or military personnel during desert training. The 2001 Arizona hospital costs were over $19 million which do not include lost time from work or the large number of persons whose infections are managed without hospitalization. Current therapies for this disease are only partially effective and in themselves are unable to eradicate the fungus from sites of infection, commonly resulting in relapses when treatment is discontinued. Nikkomycin Z is a chitin synthase inhibitor with its greatest in vitro activity against Coccidioides. It is very effective as oral experimental therapy in mice with coccidioidomycosis. Notably, nikkomycin Z treatment resulted in sterilization of the murine lesions. If this effect could also be produced in patients when administered early after infection, nikkomycin Z could eliminate the progressive, debilitating, and sometimes lethal forms of disease. Previously, a pharmaceutical company had filed an IND with the FDA, and by 1997 had completed an initial Phase 1 (single-dose) safety trial. Nikkomycin Z was sold but development was halted in 1996, solely due to financial reasons. In 2005, the University of Arizona acquired the rights, is now the sponsor of the existing IND, and intends to continue nikkomycin Z development. The investigators propose to first develop an overall drug development plan for nikkomycin Z as a therapy for coccidioidomycosis. Using existing supplies of nikkomycin Z, they propose to conduct a Phase 1/2 study in patients with uncomplicated, usually self-limited, coccidioidal pneumonia. The primary objective of the study is to evaluate safety, pharmacokinetics, and metabolism of nikkomycin Z administered for two weeks as repeated oral doses. A secondary objective is to collect exploratory observations regarding the possible therapeutic effect of nikkomycin Z. Using pharmacokinetic and pharmacodynamic analyses of data collected during this dose escalation stage, modeling and clinical trial simulations will be undertaken to select a single dose for administration to additional subjects. By carrying out the proposed work, the investigators will resume the clinical development of nikkomycin Z as a potentially curative therapy for coccidioidomycosis so that it may become a candidate for final commercial development.